Simons V M
Fortschr Med. 1995 Nov 10;113(31):441-2.
With the aim of investigating the transport and metabolism of amyloid precursor protein (APP) in neurons, APP was expressed in neurons from the hippocampus using the Semliki-Forest virus vector. It was found that APP in the cell migrates from the nucleus into the axons and from there into the dendrites. During this migration, human APP is split at the total of six places, resulting in particular in the formation of beta A4 amyloid peptide. A greater production of beta A4 was observed in persons with inherited forms of Alzheimer's disease. In rat APP, in contrast, the amount of beta A4 secreted is clearly reduced. These findings suggest that beta A4 plays a central role in the genesis of the disease. The experimental methods open up the possibility of developing and testing therapeutic approaches to Alzheimer's disease.
为了研究淀粉样前体蛋白（APP）在神经元中的运输和代谢，利用Semliki森林病毒载体在海马体的神经元中表达APP。结果发现，细胞中的APP从细胞核迁移到轴突，再从轴突迁移到树突。在这个迁移过程中，人类APP在总共六个位点被切割，特别导致了βA4淀粉样肽的形成。在患有遗传性阿尔茨海默病的患者中观察到βA4的产生更多。相比之下，在大鼠APP中，分泌的βA4量明显减少。这些发现表明βA4在该疾病的发生中起核心作用。这些实验方法为开发和测试针对阿尔茨海默病的治疗方法开辟了可能性。
